The objective of this project is to study the role of a novel family of frizzled-like genes in skeletal development, regeneration and disease. The discovery of a novel gene designated frzb in our laboratory and the dynamics of its expression pattern predominantly restricted to the developing skeleton during human embryonic development, presents us with a unique opportunity to study a complete new class of genes intimately involved in skeletal morphogenesis. Frzb is related to the Drosophila polarity gene frizzled, which encodes an integral membrane protein. This locus is required for the cellular response to a tissue polarity signal. Strong frizzled mutations are associated with random orientation of wing hairs in the fruit fly. The study of this group of polarity determining genes should allow us to further define the cell surface proteins/membrane receptors, their ligands and signal transduction pathways directly involved in the patterning process during the development of skeletal structures.